The goal of my research program is to investigate the mechanisms of human respiratory diseases to facilitate the discovery and development of novel therapies targeted to specific subsets of patients most likely to benefit. Asthma is a heterogeneous disorder on molecular, pathophysiological, and clinical levels, hence a therapeutic candidate directed against a given molecular target may be relevant to certain asthma patients but not to others. However, current guidelines for standard-of-care asthma therapy are empirical and based on clinical presentation rather than on the underlying biology of disease. Through exploratory studies in human asthma patients, my laboratory has applied innovative molecular biology and data analysis techniques to identify a molecular basis for asthma heterogeneity and discovered, developed assays for, and validated noninvasive biomarkers that reflect this heterogeneity. We have successfully used these biomarkers to predict which patients were most likely to show benefit in clinical trials of lebrikizumab, a humanized monoclonal antibody against IL13, which represents a significant advance in personalized treatment for severe asthma. Using this phenotypic information, we have identified new therapeutic targets currently under investigation for other subsets of asthma patients. We have also discovered candidate therapeutic targets and biomarkers of pathway activity and disease progression in idiopathic pulmonary fibrosis, which are currently under investigation in clinical studies of multiple therapeutic candidates. In addition to supervising the research in my laboratory, I lead a department of 10 research laboratories responsible for target discovery and preclinical therapeutic development in inflammatory, autoimmune, fibrotic, and ophthalmic diseases.
Joseph R. Arron, MD, PhD